Purpose: to perform an external validation of our predictive model to rule out pheochromocytoma (PHEO) based on unenhanced CT in a cohort of patients with PHEOs and adenomas who underwent adrenalectomy. Methods: The predictive model was previously developed in a retrospective cohort of 1131 patients presenting with adrenal lesions. In the present study, we performed an external validation of the model in another cohort of 214 patients with available histopathological results. Results: For the external validation, 115 patients with PHEOs and 99 with adenomas were included. Our previously described predictive model combining the variables of high lipid content and tumor size in unenhanced CT (AUC-ROC: 0.961) had a lower diagnostic accuracy in our current study population for the prediction of PHEO (AUC: 0.750). However, when we excluded atypical adenomas (with Hounsfield units (HU) > 10, n = 39), the diagnostic accuracy increased to 87.4%. In addition, in the whole cohort (including atypical adenomas), when MRI information was included in the model, the diagnostic accuracy increased to up to 85% when the variables tumor size, high lipid content in an unenhanced CT scan, and hyperintensity in the T2 sequence in MRI were included. The probability of PHEO was <0.3% for adrenal lesions 10 HU and without hyperintensity in T2. Conclusion: Our study confirms that our predictive model combining tumor size and lipid content has high reliability for the prediction of PHEO when atypical adrenal lesions are excluded. However, for atypical adrenal lesions with >10 HU in an unenhanced CT scan, MRI information is necessary for a proper exclusion of the PHEO diagnosis.

Background/Objectives: Type 1 diabetes (T1D) is a heterogeneous disease in terms of clinical presentation, treatment requirements, and risk of complications. The identification of biological endotypes and clinical phenotypes has been proposed to support precision medicine approaches. We aimed to assess the prevalence and clinical characteristics of age-at-diagnosis-based endotypes, adult-onset phenotypes, and insulin-resistant phenotypes in a real-world cohort of adults with T1D. Methods: We conducted a single-center, observational, cross-sectional study including adults (≥18 years) with clinically confirmed T1D under active follow-up. Clinical, metabolic, and treatment-related variables were analyzed across predefined age-at-diagnosis-based endotypes and clinical phenotypes. Results: A total of 868 patients were included (median age 49 years; diabetes duration 23 years; age at diagnosis 20 years; 51.5% women). Continuous subcutaneous insulin infusion (CSII) was used by 20.4% of patients, and continuous glucose monitoring (CGM) was used by 95.3%. Mean HbA1c was 7.47%, with a median time in range (TIR) of 63%. The prevalence of age-at-diagnosis-based endotype 1 (ED1) was 11.8%, adult-onset phenotype was 31.3%, and insulin-resistant phenotype was 7.3%. No major differences in glycemic control were observed across age-at-diagnosis-based endotypes. Associations between endotypes and treatment-related variables were largely explained by current age and diabetes duration. In contrast, the adult-onset phenotype was independently associated with lower TIR, higher time above range, lower use of CSII, and greater use of adjunctive therapies. The insulin-resistant phenotype was associated with higher HbA1c, lower TIR, and greater therapeutic complexity. Conclusions: Adult T1D shows marked heterogeneity. In this real-world cohort, age-at-diagnosis-based endotypes were not independently associated with major clinical differences after adjustment for current age and diabetes duration. In contrast, adult-onset and insulin-resistant phenotypes identified subgroups with poorer glycemic control and greater therapeutic complexity.